Impact of the junior doctors' industrial action on the emergency eye department in a large tertiary ophthalmic hospital: the Manchester experience.

PURPOSE: To assess the impact of the junior doctors' industrial action on one of the largest emergency eye departments (EED) in the United Kingdom. METHODS: We compared staff allocation, patient presentation, time in streaming, time in the department, the Manchester Triage System (MTS) score, number of eye emergencies and follow-up care of patients who attended the EED in the Manchester Royal Eye Hospital (MREH) during the 3-day industrial action (13-15 March 2023) compared with control periods 2 weeks before and 2 weeks after the industrial action. RESULTS: During the industrial action, there were almost 1.5 times more staff allocated to EED with a near doubling of the senior workforce. There was no difference in patient presentation, MTS score, number of eye emergencies or patient follow-up during the industrial action. However, patients had significantly less time in streaming (p < 0.001) and in the department (p < 0.001) during the industrial action compared to control periods. CONCLUSION: Emergency ophthalmic patient care was not compromised during the industrial action due to the reallocation of the workforce to EED. The results of this study may help in the planning of ophthalmic eye-care services in the event of future industrial actions.

Multiplexed Conformationally Selective, Localized Gas-Phase Hydrogen Deuterium Exchange of Protein Ions Enabled by Transmission-Mode Electron Capture Dissociation.

In this article, we present an approach for conformationally multiplexed, localized hydrogen deuterium exchange (HDX) of gas-phase protein ions facilitated by ion mobility (IM) followed by electron capture dissociation (ECD). A quadrupole-IM-time of flight instrument previously modified to enable ECD in transmission mode (without ion trapping) immediately following a mobility separation was further modified to allow for deuterated ammonia (ND3) to be leaked in after m/z selection. Collisional activation was minimized to prevent deuterium scrambling from giving structurally irrelevant results. Gas-phase HDX with ECD fragmentation for exchange site localization was demonstrated with the extensively studied protein folding models ubiquitin and cytochrome c. Ubiquitin was ionized from conditions that stabilize the native state and conditions that stabilize the partially folded A-state. IM of deuterated ubiquitin 6+ ions allowed the separation of more compact conformers from more extended conformers. ECD of the separated subpopulations revealed that the more extended (later arriving) conformers had significant, localized differences in the amount of HDX observed. The 5+ charge state showed many regions with protection from HDX, and the 11+ charge state, ionized from conditions that stabilize the A-state, showed high levels of deuterium incorporation throughout most of the protein sequence. The 7+ ions of cytochrome c ionized from aqueous conditions showed greater HDX with unstructured regions of the protein relative to interior, structured regions, especially those involved in heme binding. With careful tuning and attention to deuterium scrambling, our approach holds promise for determining region-specific information on a conformer-selected basis for gas-phase protein structures, including localized characterizations of ligand, epitope, and protein-protein binding.

Complete manuscript title: Neurological complications from sinugenic orbital cellulitis.

INTRODUCTION: This study was undertaken with an aim to identify any common factors or trends among patients of orbital cellulitis that developed neurological complications. METHODS: A 24-month retrospective review of patients was undertaken to include those showing clinical deterioration and neurological complications on radiological imaging, after being treated for orbital cellulitis at Manchester Royal Eye Hospital. The study specifically looked at the site of orbital collection, sinus involvement, types of neurological complications and whether these were detected at initial presentation, surgical input and microbiology findings. RESULTS: Nine patients (9/26) developed associated neurological complications during the study period. (February 2018 and January 2020) This included subdural empyema in six patients; leptomeningeal enhancement in two and septic emboli in one patient. All the patients had associated significant pan-sinusitis at initial presentation. Neurological complications were detected in three patients at the time of admission and after clinical deterioration and further investigations in the rest. CONCLUSION: A superior orbital abscess and Streptococcus mileri infection had higher risk of neurological complications. It is worth debating whether patients with chronic sinusitis who develop orbital cellulitis need earlier surgical input rather than a conservative treatment. Patients who fail to improve clinically need to be re-imaged to look for possible neurological complications.

Implementation of Genetic Engineering and Novel Omics Approaches to Enhance Bioremediation: A Focused Review.

Bioremediation itself is considered to be a cost effective soil clean-up technique and preferred over invasive physical and chemical treatments. Besides increasing efficiency, application of genetic engineering has led to reduction in the time duration required to achieve remediation, overcoming the so called 'Achilles heel' of Bioremediation. Omics technologies, namely genomics, transcriptomics, proteomics, and metabolomics, are being employed extensively to gain insights at genetic level. A wise synchronised application of these approaches can help scrutinize complex metabolic pathways, and molecular changes in response to heavy metal stress, and also its fate i.e., uptake, transport, sequestration and detoxification. In the present review, an account of some latest achievements made in the field is presented.

Patterns of attendances to the hospital emergency eye care service: a multicentre study in England.

BACKGROUND/OBJECTIVES: To characterise the patterns of presentation and diagnostic frequencies in Hospital Emergency Eye Care Services (HEECS) across 13 hospitals in England. METHODS: Retrospective, cross-sectional, observational multi-centre (n = 13) study to assess HEECS attendances over a 28-day study period. Data derived included: number of consecutive attendances, patient demographics and diagnoses. Age and gender variations, the impact of day of the week on attendance patterns, diagnostic frequencies and estimates of the annual incidence and attendance rates were evaluated. RESULTS: A total of 17,667 patient (mean ± standard deviation age = 49.6 ± 21.8 years) attendances were identified with an estimated HEECS annual new attendance rate of 31.0 per 1,000 population. Significantly more females (53%) than males (47%) attended HEECS (p < 0.001). Female attendances were 13% higher in those ≥50 years of age. Weekends were associated with a significant reduction in attendances compared to weekdays (χ2 = 6.94, p < 0.001). Among weekdays, Mondays and Fridays were associated with significantly higher attendances compared with midweek (χ2 = 2.20, p = 0.032). Presenting pathologies involving the external eye, cornea and conjunctiva accounted for 28.6% of the caseload. CONCLUSION: This is the largest multicentre study assessing attendance patterns in HEECS in England. We have, for the first time, observed a "weekend effect" in relation to attendance to HEECS. Differences in health-seeking behaviour and lack of awareness of HEECS weekend services may be partly attributed to the differences observed. Our findings, along with the type of presentations, have the potential to guide commissioners with future planning of HEECS.

Mechanistic studies of dinucleotide and oligonucleotide model cyclobutane pyrimidine dimer (CPD) DNA lesions under alkaline conditions.

Cyclobutane pyrimidine dimers (CPDs) are the most abundant mutagenic DNA lesions formed in mammalian cells upon exposure to UV-B radiation (280-315 nm) in sunlight. These lesions are thought to be chemically stable and to withstand high concentrations of acids and bases.While earlier investigations of DNA lesions containing saturated pyrimidines have shown that the C4 carbonyl is a potential target of nucleophilic attack, similar reactions with thymine nucleobase model CPDs clearly showed that the cis-syn CPD (major isomer) is stable in the presence of a high concentration of alkali at room temperature. Here is described the alkaline reactivity of these lesions when contained within a dinucleotide CPD model system. Results using cis-syn CPD formed from dinucleotide 5'-TpT-3' combined with [18O]-labelling indicated that CPD undergoes a water addition at the C4=O groups of these now saturated rings. The intermediate formed, however, completely reverts to the starting lesion. Along with confirming the target of water addition within CPD lesions, it was also determined that the two C4 carbonyls present on adjacent saturated pyrimidine rings of the photolesion undergo water exchange at different rates (3' > 5'). Moreover, the difference in reactivity exhibited by these two positions is not limited to a dinucleotide and was observed also in oligonucleotides. Overall, a full understanding of the chemistry of CPD lesions is crucial to our knowledge of naturally-occuring DNA modifications and may lead to further insight into their detection, modification, and biochemical recognition & repair.

Harnessing Pisum sativum-Glomus mosseae symbiosis for phytoremediation of soil contaminated with lead, cadmium, and arsenic.

This study investigates the impact of Glomus mosseae on heavy metal(loid) (HM) uptake efficiency of pea (Pisum sativum L.) plants along with physiological and biochemical parameters. Plants were grown in soil spiked with HMs (Pb and As: 50 and 100 mg kg-1; Cd: 25 and 50 mg kg-1) and a multi-metal(loid) (Mm: Pb + Cd + As) combination, inoculated/non-inoculated with G. mosseae. A dose-dependent increase in HM accumulation was observed in plants upon harvest at 60 days. Plant growth, concentration of photosynthetic pigments, total nitrogen, and carbohydrates reduced, whereas enzymatic [catalase (CAT), superoxide dismutase (SOD), and ascorbate peroxidase (APX)] and non-enzymatic (proline and total phenolics) antioxidants increased upon HM stress. Inoculation with G. mosseae led to an increase in plant growth, concentration of photosynthetic pigments, carbohydrate, nitrogen, and defence antioxidants (whereas proline decreased) which was statistically significant (p ≤ 0.05). This symbiosis can be applied for onsite remediation of Pb and Cd contaminated soil by virtue of accumulation efficiency and adaptive response of pea plants inoculated with G. mosseae. Since the amount of HMs in edible parts exceeded the maximum permissible limits recommended by FAO/WHO, pea must not be cultivated in HM-contaminated soil for agricultural purpose due to associated toxicity. Novelty statement  To our knowledge, phytoremediation potential of Pea in synchronization with Glomus mosseae has not been evaluated previously. This study highlights: • Pea-AMF symbiosis can be applied for Pb and/or Cd phytoremediation. • Target Hazard Quotient >1 for Pb, Cd and As; caution to food chain exposure required. • Nonenzymatic (proline, TPC) and enzymatic (CAT, SOD, APX) antioxidants play a key role in ROS detoxification.

Metal(loid) induced toxicity and defense mechanisms in Spinacia oleracea L.: Ecological hazard and Prospects for phytoremediation.

A pot study was conducted to assess the phytoremediation potential of Spinach plants along with their physiological and biochemical response when grown in soil contaminated with heavy metal(loid)s (HMs). Plants were grown under different doses of Pb, Cd and As; and their metal(loid) accumulation efficiency was studied upon harvest; expressed in terms of bioabsorption coefficient (BAC), bioconcentration factor (BCF) and translocation factor (TF). Results showed significant (p ≤ 0.05) difference in physiological and biochemical mechanisms of plants as detected through decrease in concentration of cellular constituents (pigments, carbohydrates, total nitrogen content); and increase in antioxidants (both enzymatic and non-enzymatic). Despite of accumulating high amount of HMs in tissues, no visible signs of toxicity were seen; and hence the efficient survival and defense mechanism shown by spinach plants conclude that they are a viable option to be used for phytoremediation of sites contaminated with Cd and Pb. Since the content of Cd and Pb in edible part was higher than safe limits prescribed by USEPA, the present investigation also highlights the ecological hazards that may result upon cultivation of spinach in contaminated soil for agricultural purpose; or its accidental exposure to food chain when grown for phytoremediation.

EDTA-Assisted Metal Uptake in Raphanus sativus L. and Brassica oleracea L.: Assessment of Toxicity and Food Safety.

A study was conducted to determine the effect of ethylenediaminetetraacetic acid (EDTA) on phytoextraction potential of radish and cabbage. Plant biomass, photosynthetic pigments, proline and phenolics were significantly affected by the accumulation of heavy metals (HM). The metal uptake potential was increased significantly by the application of EDTA. Target hazard quotient (THQ) associated with exposure of these contaminants to food chain was calculated. Agronomic interventions to increase mineral levels in crops often increases the leaf concentrations only, the mineral concentration in edible portions are not increased at desired level due to low mobility of Zn in phloem. Since the leaves of both these crops are edible and a component of staple vegetarian diet, biofortification through Zn present in soil and its solubilization and mobilization through chelators can be implemented. However in no such instance these crops should be consumed when grown on Pb contaminated soil due to associated hazards.

Effect of Glomus mossae on accumulation efficiency, hazard index and antioxidant defense mechanisms in tomato under metal(loid) Stress.

In the present study, the phytoremedation potential along with growth, physiological and biochemical response of tomato (Solanum lycopersicum) was assessed under heavy metal(loid) (HM) and arbuscular mycorrhizal fungus (AMF) amendment. Effect of AMF on uptake and accumulation of metal(loid)s was assessed and accumulation characteristics were expressed in terms of bioabsorption coefficient (BAC), bioconcentration factor (BCF), translocation factor (TLF) and transfer factor (TF). Results showed that AMF-inoculated plants showed not only a better growth, chlorophyll content, strengthened non-enzymatic and enzymatic defense mechanism, but also accumulated higher concentration of metal(loid)s. The correlation between biochemical and physiological parameters was significant at 0.01 level. A significant difference (p ≤ 0.001) in antioxidant enzyme activity was found on increasing metal(loid) dose and application of AMF. The accumulation of Cd and Pb in edible part exceeded the chronic reference dose stated by USEPA. The target hazard quotient (THQ) was >1 for Cd and Pb, whereas <1 for As. The study shows that tomato has good potential as Cd and Pb phytoremediator, hence must not be consumed when grown on Cd or Pb contaminated sites.

Assessment of edibility and effect of arbuscular mycorrhizal fungi on Solanum melongena L. grown under heavy metal(loid) contaminated soil.

Arbuscular mycorrhizal fungi (AMF) aids in plant establishment at heavy metal(loid) (HM) contaminated soils, strengthening plant defense system along with promoting growth. A pot experiment was carried out to evaluate the effect of AMF on eggplants grown under HM stress. Further, the potential health risks of HM exposure to the humans via dietary intake of eggplant were also estimated. Results showed that AMF application improved growth, biomass and antioxidative defense response of plants against HM stress. Significant difference (p ≤ 0.001) in parameters under study was found on increasing metal dose and on application of AMF. Among metal(loid)s maximum uptake was recorded for Pb (29.64mgkg-1 in roots; 23.08mgkg-1 in shoot) followed by As (3.84mgkg-1 in roots; 8.20mgkg-1 in shoot) and, Cd (0.96mgkg-1 in roots; 2.12mgkg-1 in shoot). Based on the accumulation of HM in edible part, Hazard Quotient (HQ) was calculated. HQ was found to be > 1 for Pb, which highlights the risks associated with consumption of Eggplants grown on Pb contaminated soil. However this potential, which was further enhanced by application of AMF, can be harnessed for on-site remediation of Pb contaminated soils. The content of Cd and As in the edible part was found to be within safe limits (HQ < 1) when compared to chronic reference dose stated by USEPA.